A short evolutionary history of FSH-stimulated spermatogenesis

Huhtaniemi, Ilpo

doi:10.14310/horm.2002.1632

Cited by 57 publications

(55 citation statements)

References 84 publications

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“…The alignment of mLhr and rLhr revealed that the two molecules are overall structurally similar (94.2% identity), reflecting their evolutionary closeness [2, 10], while lower sequence identity was observed by mouse/rat versus human receptor comparison (mLhr versus LHCGR = 81.93%; rLhr versus LHCGR = 83.93%), especially at the hinge region (Table 1). …”

Section: Resultsmentioning

confidence: 99%

“…LH is produced by the pituitary in a pulsatile fashion, inducing ovulation and maintenance of the corpus luteum in females. In adult males, LH regulates spermatogenesis acting on Leydig cells located in the testes, by controlling testosterone production [2, 3]. hCG is the primate-specific pregnancy hormone produced by trophoblast cells [4].…”

Section: Introductionmentioning

confidence: 99%

“…spermatogenesis, are critically depending on testosterone in mice and rats [2]. The steroid hormone is produced by Leydig cells expressing the murine LH receptor (mLhr), upon LH stimulation.…”

Section: Introductionmentioning

confidence: 99%

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Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro

Riccetti

Pascali

Gilioli

et al. 2017

Reprod Biol Endocrinol

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BackgroundHuman luteinizing hormone (LH) and chorionic gonadotropin (hCG) are glycoprotein hormones regulating development and reproductive functions by acting on the same receptor (LHCGR). We compared the LH and hCG activity in gonadal cells from male mouse in vitro, i.e. primary Leydig cells, which is a common tool used for gonadotropin bioassay. Murine Leydig cells are naturally expressing the murine LH receptor (mLhr), which binds human LH/hCG.MethodsCultured Leydig cells were treated by increasing doses of recombinant LH and hCG, and cell signaling, gene expression and steroid synthesis were evaluated.ResultsWe found that hCG is about 10-fold more potent than LH in cAMP recruitment, and slightly but significantly more potent on cAMP-dependent Erk1/2 phosphorylation. However, no significant differences occur between LH and hCG treatments, measured as activation of downstream signals, such as Creb phosphorylation, Stard1 gene expression and testosterone synthesis.ConclusionsThese data demonstrate that the responses to human LH/hCG are only quantitatively and not qualitatively different in murine cells, at least in terms of cAMP and Erk1/2 activation, and equal in activating downstream steroidogenic events. This is at odds with what we previously described in human primary granulosa cells, where LHCGR mediates a different pattern of signaling cascades, depending on the natural ligand. This finding is relevant for gonadotropin quantification used in the official pharmacopoeia, which are based on murine, in vivo bioassay and rely on the evaluation of long-term, testosterone-dependent effects mediated by rodent receptor.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-016-0224-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro

Riccetti

Pascali

Gilioli

et al. 2017

Reprod Biol Endocrinol

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“…As described above, hormonal dominance of spermatogenesis shifted during evolution from FSH to LH [9], whereas FSH has been considered essential for induction of and qualitative and quantitative maintenance for spermatogenesis [49]. The characteristics of FSHβ KO mice were reported by Kumer et al The serum testosterone level was normal and as a result, normal male external genitalia developed.…”

Section: Fsh Stimulation Of Sertoli Cellsmentioning

confidence: 85%

“…However, findings form LuRKO mice revealed the importance of LH action for spermatogenesis. Accordingly, the main regulatory gonadotropin for spermatogenesis has been shifted from FSH dominance to LH dominance [9].…”

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confidence: 99%

Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [Review]

Shiraishi

Matsuyama

2017

Endocr J

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Abstract. Microdissection testicular sperm extraction and intracytoplasmic sperm injection have made it possible for men with non-obstructive azoospermia (NOA) to conceive a child. A majority of men cannot produce sperm because spermatogenesis per se is believed to be "irreversibly" disturbed. For these men, it has been thought that any hormonal therapy will be ineffective. Further understandings of endocrinological regulation of spermatogenesis are needed and LH or FSH receptor knock out (KO) mice have revealed the roles of gonadotropin separately. Spermatogenesis has been shown to shift during evolution from FSH to LH dominance because LH receptor KO causes infertility while FSH receptor KO does not. High concentrations of intratesticular testosterone secreted from Leydig cells, ranging from 100-to 1,000-fold higher than in the systemic circulation, has pivotal roles during spermatogenesis. This is especially important during spermiogenesis, a post-meiotic step for progression from round to elongating spermatids. Sertoli cells are the target of FSH and have numerous androgen receptors, indicating that Sertoli cells are regulated by FSH and the paracrine functions of testosterone. In combination with Leydig cell-derived growth factors, particularly epidermal growth factor-like growth factors, Sertoli cells support spermatogenesis, especially at proximal levels of spermatogenesis (e.g., spermatogonial proliferation). Taken together, the current knowledge from human studies indicating that testosterone optimization by clomiphene, hCG and/or aromatase inhibitors and high dose hCG/FSH treatment can, at least in part, improve spermatogenesis in NOA. Accordingly hormonal therapy may open a therapeutic window for sperm production in selected patients.Key words: Non-obstructive azoospermia, Testicular sperm extraction, Gonadotropin, Hormonal therapy FIFTEEN to twenty percent of couples are categorized as infertile. Generally, a male-related factor is involved in more than half of the cases. Among male-related factors, approximately 10 % of cases are diagnosed as non-obstructive azoospermia (NOA). NOA is the most prevalent and challenging form of azoospermia for both patients and physicians because spermatogenesis per se is believed to be "irreversibly" disturbed and it has been thought that any medical therapy, including hormonal therapy, will be ineffective. Unlike oogenesis, where there is a substantial amount of information regarding endocrine regulation, information regarding spermatogenesis, especially in humans, is very limited.Along with the development and availability of intracytoplasmic sperm injection (ICSI) since the 1990's, the goal of NOA treatment has not necessarily required many sperm in the ejaculate for assisted insemination or in-vitro fertilization. However, a single sperm is theoretically enough for ICSI to perform infertility treatment. As a result, the established surgical approach to retrieve sperm directly from the testis was called microdissection testicular sperm extraction (micro-TESE) [1]....

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